ACE2 and SARS-CoV-2 Spike Protein

By SWA

ACE2 stands for angiotensin-converting enzyme 2. 

Explanation in short: 

It is an enzyme that is attached to the cell membranes of cells located in the lungs, arteries, heart, kidney, and intestines. ACE2 normally plays a crucial role in the renin-angiotensin system—a hormone system that regulates blood pressure and fluid balance. Importantly, ACE2 also acts as a receptor for some coronaviruses, including the virus responsible for COVID-19, SARS-CoV-2, facilitating viral entry into cells.

Testing for the presence and activity of ACE2 (angiotensin-converting enzyme 2) can be approached in several ways, depending on whether you are examining its expression in tissues, its protein levels, or its enzymatic activity. Here’s how these tests are typically conducted:

  1. Gene Expression Analysis:

    • RT-PCR (Reverse Transcription Polymerase Chain Reaction): This method is used to detect the mRNA expression of ACE2, indicating how much of the enzyme is being produced at the genetic level. It involves converting RNA into DNA and then amplifying specific DNA targets to measure their abundance.
    • Northern Blotting: This technique can also be used for assessing mRNA levels, though it is less common than RT-PCR.

  2. Protein Detection and Quantification:

    • Western Blot: This method is used to detect ACE2 protein in tissue extracts. It involves separating proteins by gel electrophoresis, transferring them to a membrane, and then using an antibody specific to ACE2 to detect its presence.
    • ELISA (Enzyme-Linked Immunosorbent Assay): This is a common biochemical technique used to measure the concentration of ACE2 protein in biological fluids. It uses antibodies that specifically bind to ACE2.
    • Immunohistochemistry: This technique is used to visualize ACE2 expression in tissue sections. It involves staining tissues with antibodies specific to ACE2 and examining them under a microscope.

  3. Enzymatic Activity Assay:

    • ACE2 Activity Assay: This test measures the enzymatic activity of ACE2 in converting its substrate. Typically, synthetic peptides that mimic the natural substrate of ACE2 are used, and the product of the enzymatic reaction is measured. This can be quantified using various biochemical techniques like colorimetric or fluorescent assays.

Each of these methods provides different types of information about ACE2, such as how much of it is being made, its presence and localization in tissues, and its functional activity. The choice of method depends on the specific research question or clinical diagnostic need.

A list of publication about SARS-CoV-2 Spike Protein and ACE2. 

Autoantibodies to ACE2 and immune molecules are associated with COVID-19 disease severity
https://pubmed.ncbi.nlm.nih.gov/38491326/

ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023728/

ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089194/

Neurological damages in COVID-19 patients: Mechanisms and preventive interventions
https://onlinelibrary.wiley.com/doi/10.1002/mco2.247

ACE2 is a type I integral membrane protein with its active site domain exposed to the extracellular surface of endothelial cells and the renal tubular epithelium.

ACE2 hydrolysis of Ang A generates the peptide alamandine that acts through the Mas-related gene receptor MrgD14. ACE2 is located on the X chromosome, women and men were analysed separately.

Clinical Utility of Amplification Refractory Mutation System-Based PCR and Mutation-Specific PCR for Precise and Rapid Genotyping of Angiotensin-Converting Enzyme 1 (ACE1-rs4646996 D>I) and Angiotensin-Converting Enzyme 2 (ACE2-rs4240157T>C) Gene Variations in Coronary Artery Disease and Their Strong Association with Its Disease Susceptibility and Progression
https://pubmed.ncbi.nlm.nih.gov/35741131/

13 publication on ACE2 : Intron Variant:
https://www.ncbi.nlm.nih.gov/snp/rs4240157#publications

The interaction between ACE2, zinc and copper:

COVID-19: Zinc and Angiotensin-Converting Enzyme 2 (ACE2) Deficiencies as Determinants of Risk and Severity of Disease: A Narrative Review
https://pubmed.ncbi.nlm.nih.gov/34251655/

Zn2+ and Cu2+ Interaction with the Recognition Interface of ACE2 for SARS-CoV-2 Spike Protein
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252707/

Copper levels in patients with rheumatoid arthritis
https://www.aaem.pl/Copper-levels-in-patients-with-rheumatoid-arthritis,71934,0,2.html

Genetically predicted circulating levels of copper and zinc are associated with osteoarthritis but not with rheumatoid arthritis
https://pubmed.ncbi.nlm.nih.gov/33640581/


 


 

 


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